The overall goal of this proposal is to examine the mechanisms by which triglyceride-rich lipoproteins (TGRL), and a major TGRL apoprotein (apoE), interact with the artery wall. Our preliminary data suggest that arterial endothelium must be injured before significant TGRL can enter the artery wall, lipolysis of TGRL may injure endothelium and apoE limits TGRL penetration into the artery wall. By using a recently developed mouse perfusion artery model, we propose to examine how TGRL interacts with the artery wall by determining: (1) The mechanisms of accumulation of TGRL on the endothelial cell luminal surface and in the artery wall. (2) The actions of lipolysis of TGRL on endothelial cell permeability properties and low-density lipoprotein (LDL) trafficking in the artery wall. (3) How apoE-associated lipoproteins bind to endothelium and if apoE isoforms (apoE3 versus apoE4) differ in their interactions with the arterial wall. Completion of these aims will greatly increase the knowledge base with regard to the effects of TGRL on vascular disease, potentially fundamentally change in the way we think about vascular disease and set the stage for the development of therapeutic strategies aimed at prevention of TGRL-induced arterial disease. [unreadable] [unreadable]